Proliferative vitreoretinopathy (PVR) is the major cause for failure of retinal reattachment surgery for rhegmatogenous retinal detachment. While its occurrence is relatively low (approximately 5-10%) PVR remains a difficult disease to treat. With the exception of surgical intervention, for which 20-40% of the patients fail to achieve anatomical success, there is no treatment for individuals afflicted with PVR, and hence there is an acute need to develop non-surgical-based therapies for patients with PVR. The overall goal of this proposal is to confirm and extend our recent observation that a certain class of FDA-approved agents for ocular diseases protected rabbits from developing PVR without any detectable impact on the overall morphology or function of the retina. In this project we will compare the ability of a panel of FDA-approved agents to protect rabbits from developing PVR. Two PVR models will be used; the most common and aggressive (injection of fibroblasts), and the more physiological (injection of retinal pigment epithelial cells). We will complement these animal studies with tissue culture experiments that compare the panel of FDA-approved agents to block vitreous-driven cellular responses (proliferation, survival, migration and contraction) tht are intrinsic to PVR. Our findings will determine which agent prevents experimental PVR best, and begin to identify the cellular responses that are being targeted. We expect that the results of the proposed studies will have a sustained, powerful influence on the development of approaches to prevent PVR for the following two reasons. First, there are currently no strategies available to reduce a patient's risk of developing PVR. Identifying agents that prevent animals from developing PVR will begin to address this stumbling block to protecting patients from succumbing to PVR. Second, the strategy of focusing on options that are FDA-approved is the fastest way to translate our findings to the clinic.